The long term goals are to obtain as complete a description as possible of the electrophysiological behavior of four channels in the cardiac sarcolemmma (SL). These are the Na, Ca, inwardly rectifying K (IRK) and transient K (TK) channels. For Na channels, particular emphasis will be placed upon the slow component of inactivation and its significance in the interpretation of single channel results. In addition the effects of antiarrhythmic agents and ischemia (specifically pH changes) upon Na channel behavior, will be examined. For Ca channels, features specific for cardiac function will be studied. How do cardiac Ca channel agonists work, how does norepinephrine increase Ca currents, and how is cardiac SL Ca current linked to cardiac SR Ca release? For IRK, I am interested in both the effects of ionic blockers including K ion, on opening probability, and on channel selectivity. Two possible regulatory components of TK, potential and Cai will be studied and the possible relationship between TK and IRK investigated. Single channels will be isolated using the patch gigaseal method and appropriately selected solutions. The usual patch configurations will be employed. Currents from larger numbers of channels will be studied using outside-out patches, or whole cell currents. For the latter, a single electrode voltage clamp method in which potential is measured directly will be used, although the I-V converter patch clamp method may be used as well. In both cases the patch pipette will be perfused. Impedance and noise measurements will also be done. A combined approach is necessary because single channel studies are bandwidth-limited due to low signal-to-noise for Ca and Na channels particularly. Computer programs have been developed to automate data analysis. In addition models of channel behavior can be analyzed. These are sequential schemes in which transitions between states form a Markov chain. Identifiability methods are used to determine the data sets necessary for evaluating a particular model.